Lazertinib 80mg tablets

ObjectiveTo evaluate the risk of cardiovascular adverse events associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with EGFR-mutated non-small cell lung cancer (NSCLC).DesignSystematic review and network meta-analysis.Data sourcesPubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and three clinical trial registries, from inception to 20 November 2024.Study selectionRandomised controlled trials comparing EGFR tyrosine kinase inhibitor monotherapy with placebo or other treatments in patients with EGFR-mutated NSCLC.Data extraction and synthesisPairs of reviewers extracted data and assessed risk of bias. A random effects network meta-analysis using a frequentist approach compared adverse drug reactions across different treatments. Certainty of evidence was evaluated using the confidence in network meta-analysis approach. Pairwise meta-analyses were done to compare the three generations of EGFR tyrosine kinase inhibitors.ResultsThe network meta-analysis comprised 89 randomised controlled trials involving 29 813 participants, mean follow-up 2.18 years. Compared with placebo, both first generation (odds ratio 1.51, 95% confidence interval 1.01 to 2.26; high certainty; pooled incidence 3.2%) and third generation EGFR tyrosine kinase inhibitors (2.18, 1.46 to 3.27; high certainty; 9.5%) were associated with increased risks of cardiac adverse events. Among third generation inhibitors, osimertinib (2.53, 1.53 to 4.19; high certainty; 8.9%) and lazertinib (2.84, 1.17 to 6.91; moderate certainty; 2.7%) were associated with cardiac adverse events. Combined therapies, such as antiangiogenesis with erlotinib or gefitinib, were associated with vascular adverse events (high certainty), whereas antiangiogenesis with osimertinib was associated with cardiovascular adverse events (moderate to high certainty). Also, the risk of arrhythmias was significantly higher with third generation inhibitors (3.26, 1.83 to 5.81; high certainty; 7.3%), such as osimertinib alone (3.35, 1.75 to 6.40; high certainty; 6.2%) and in combination with antiangiogenesis. Almonertinib was associated with vascular toxicity. In pairwise meta-analysis, third generation inhibitors were associated with higher risks of any grade and grade ≥3 cardiovascular adverse events compared with first generation inhibitors.ConclusionsIn patients with EGFR-mutated NSCLC, first and third generation EGFR tyrosine kinase inhibitors, as well as combination therapies with antiangiogenesis, were associated with increased risks of cardiovascular adverse events. Risks were significantly higher with third generation compared with first generation inhibitors.Systematic review registrationPROSPERO CRD42023433003.

Abstract licence: CC BY-NC

Background and Objective Epidermal growth factor receptor (EGFR) mutations are a common driver of oncogenesis in non-small cell lung cancer (NSCLC). Lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), has shown promise as a first-line treatment for patients with locally advanced or metastatic EGFR-mutated NSCLC. However, the comparative efficacy and safety of lazertinib in this setting have not been thoroughly investigated. This study aims to evaluate the efficacy and safety of lazertinib for EGFR-mutated locally advanced NSCLC. Method This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We performed a search of PubMed, ProQuest, EBSCO, and ScienceDirect to identify eligible studies based on the PICOTS-SD criteria. The meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse effects was performed using RevMan 5.4 software. Results This review included a total of three randomized controlled trials. The pooled analysis revealed significant differences in PFS, with a hazard ratio (HR) of 0.44 (95% confidence interval [CI]: 0.37–0.53). However, OS showed no significant differences, with an HR of 0.82 (95% CI: 0.64–1.06). Paresthesia occurred significantly more frequently in the lazertinib group (odds ratio [OR]: 11.30; 95% CI: 7.30–17.49). In contrast, the incidence of diarrhea and increases in Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) levels were significantly higher in the gefitinib group, with ORs of 0.52 (95% CI: 0.39–0.70), 0.35 (95% CI: 0.25–0.50), and 0.32 (95% CI: 0.22–0.47), respectively. Conclusion Lazertinib demonstrated a greater therapeutic benefit for patients with EGFR-mutated advanced NSCLC compared to first-generation EGFR-TKIs. Further research is needed to validate these findings.

Abstract licence: CC BY-NC-SA 4.0

BackgroundHead‑to‑head comparisons among first‑line third‑generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR‑mutated unresectable non-small cell lung cancer (NSCLC) are nearly absent. This network meta‑analysis compares the efficacy and safety of all available agents and provide evidence-based references for clinical decision-making.MethodsWe searched PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 2026. Eligible studies were randomized controlled trials (RCTs) enrolling patients with advanced EGFR-mutated NSCLC receiving first-line third-generation EGFR-TKIs compared with first-generation EGFR-TKIs. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2 tool. The primary efficacy outcome was progression-free survival (PFS). We performed a network meta-analysis (NMA) using a fixed-effect model and ranked treatments using surface under the cumulative ranking curve (SUCRA). The protocol was registered with PROSPERO (CRD42022349097).ResultsEleven RCTs comprising 4,663 patients were analyzed. All investigated third-generation agents (aumolertinib, osimertinib, furmonertinib, befotertinib, limertinib, rilertinib, lazertinib, and rezivertinib) demonstrated superior PFS compared to first-generation TKIs. However, no statistically significant PFS differences were observed among the third-generation agents. Similarly, no significant differences were found between third- and first-generation TKIs regarding objective response rate (ORR) or ≥ G3 treatment-emergent adverse events (TEAEs). Subgroup analyses revealed no significant PFS benefit for befotertinib over first-generation TKIs in the L858R subgroup, nor for befotertinib or furmonertinib in elderly patients.ConclusionsMost third-generation TKIs offer superior PFS compared to first-generation agents, with comparable efficacy observed across the third-generation agents. Safety profiles, specifically regarding high-grade adverse events, appear similar between third- and first-generation TKIs.

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Amivantamab, a newly introduced drug for locally advanced or metastatic NSCLC in patients with EXON-20 mutation, has shown promising results for prolonging progression-free survival and overall survival. Amivantamab's toxicities are common, especially those related to skin and infusion. However, its cardiovascular related toxicities are less examined. Therefore, the aim of this study was to perform a systematic review and concentrate available data for the cardiovascular toxicities of amivantamab in patients with NSCLC. This review was performed according to the PRISMA guidelines, and relevant studies were searched on three scientific databases, PubMed, Cochrane Library and ScienceDirect. In total, four phase-3 randomized clinical trials, three phase-1 clinical trials, and two real-world study were included in this systematic review. The results revealed that grade ≥ 3 cardiovascular toxicities are low in amivantamab monotherapy (<10 %), but their frequency increases when combined with lazertinib and overcome 20 % when amivantamab is combined with both lazertinib and chemotherapy. In addition, up to 3 % grade 5 cardiovascular events have been reported when amivantamab is combined with lazertinib. Pulmonary embolism and venous thromboembolism are the most common cardiovascular toxicities reported for amivantamab, and their risk increases when combined with lazertinib. These results indicate that amivantamab may be cardiotoxic, especially when combined with lazertininb, and cardioprotection should be considered in patients under amivantamab treatment.

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